Programmed Cellular Immunotherapies

Transcription

1 Better Cells For Better Therapies Programmed Cellular Immunotherapies Corporate Overview January

2 Forward-Looking Statements This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company's advancement of and plans related to the Company's product candidates, clinical studies, and research and development programs, the Company's progress and plans for its clinical investigation of ProTmune, FATE-NK100 and its induced pluripotent stem cell-derived product candidates, the timing for initiation of the Company's planned clinical trials of its product candidates, the therapeutic potential of the Company's product candidates, the scope and enforceability of the Company s intellectual property portfolio, and the Company's financial condition. These and any other forward-looking statements in this presentation are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in prior studies, including preclinical studies of ProTmune, FATE-NK100 and its induced pluripotent stem cell-derived product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay in the enrollment or evaluation of subjects in any ongoing clinical studies, the risk that the Company may cease or delay preclinical or clinical development for any of its existing or future product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities and requirements for regulatory approval, difficulties or delays in subject enrollment in current and planned clinical trials, difficulties in manufacturing and supplying the Company's product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that the Company's expenditures may exceed current expectations for a variety of reasons. These statements are also subject to other risks and uncertainties as further detailed in the Company's most recently filed Form 10-Q, and subsequent periodic reports filed by the Company under the Securities Exchange Act of 1934, as amended, any of which could cause actual results to differ materially from those contained in or implied by the forward-looking statements in this presentation. The Company is providing the information in this presentation as of the date hereof and does not undertake any obligation to update any forward-looking statements contained in this presentation unless required by applicable law

3 Fate Therapeutics Mission To develop first-in-class cell-based immunotherapies for cancer and immune disorders by programming cell function and fate T cells CD34 + cells NK cells induced Pluripotent Cell Platform for off-the-shelf engineered immunotherapies - 3 -

4 Proven Role of Cells in Cancer Immunotherapy Antibody-Dependent Cellular Cytotoxicity (ADCC) Immune Checkpoint Blockade Targeted / Activated Cell Products - 4 -

5 Early Innings of Cellular Immunotherapy Development Patient-derived CAR T Cells Patient Genetic Engineering Random & Variable Cell Composition Heterogeneous Manufacturing Yield Single Patient per Run How do we Build on Early Successes and Transition From a Personalized Process to the Delivery of an Optimized Cell Product? - 5 -

6 Fate Therapeutics Juno Therapeutics Collaboration Patient-derived CAR T Cells Broad Research Collaboration Combining Fate s Small Molecules with Juno s Industry-leading CAR T-Cell Franchise May 2015: Four-year research collaboration to identify small molecule modulators that enhance the properties of T cells Juno to fund all collaboration activities Juno has exclusive option to license small molecule modulators for genetically-engineered CAR / TCR T-cell therapies against selected tumor-associated antigen targets Juno option excludes license for all ipsc-derived cell therapies (including CAR / TCR T-cell therapies) Significant economic opportunity $5M upfront payment, plus purchase of 1M shares of FATE c/s at $8.00 per share ~$500M in target selection fees / milestones across first five modulated products Single-digit royalties on sales of modulated products - 6 -

7 Better Cells for Better Therapies Our Approach to Cellular Immunotherapy Programmed Donor Cell Products Off-the-Shelf Cell Products Donors Cells from healthy donors with selected traits ipsc Line Renewable pluripotent cell line with engineered functionality Molecules Ex vivo cell modulation to program biological properties Cell Bank Ex vivo expansion / differentiation to derive clonal cell populations Cell products programmed for enhanced therapeutic function Off-the-shelf engineered cell products for 1000s of patients Cell Therapies Cell Therapies - 7 -

8 Fate Therapeutics First-in-Class Cellular Immunotherapy Pipeline IMMUNO-ONCOLOGY PROGRAM PRECLINICAL CLINICAL RIGHTS FATE-NK100 AML Phase 1 Worldwide FATE-NK100 Ovarian Phase 1 Worldwide FATE-NK100 Solid Tumor mab Combo Phase 1 Worldwide FT500 (ink Cell) OTS Checkpoint Inhibitor Combination Worldwide FT516 (Engineered hncd16 ink Cell) OTS Monoclonal Antibody Combination Worldwide FT538 (Engineered CD38- ink Cell) OTS Daratumumab Combination Worldwide FT819 (Engineered CAR19 it Cell) OTS Worldwide IMMUNO-REGULATION ProTmune Graft-versus-Host Disease Phase 2 Worldwide ToleraCyte Autoimmune Disorders Worldwide FT300 (imds Cell) OTS Worldwide OTS Off-the-Shelf using Clonal Master Induced Pluripotent Stem Cell (ipsc) Lines - 8 -

9 Immuno-Oncology Programs - 9 -

10 Natural Killer Cells Unique Properties Enable Off-the-Shelf Cancer Immunotherapy Effector function is not patient or single-antigen specific Multi-faceted effector function against tumor cells Use of mismatched cells has been shown to be well-tolerated / low risk of GvHD Inhibitory receptors check NK cell activation, preventing cytotoxicity towards healthy cells _ TCR Unlike T cells, NK cells do not elicit GvHD Activating receptors recognize stressed cells independent of antigen recognition Activate the adaptive immune system through cytokine release + + NK Cells CD16 Fc Receptor Potentiate tumor-specific targeting mabs (ADCC) Direct killing of target cells through granule release

11 Adaptive Memory NK Cells A Potent Subset of NK Cells with Unique Anti-tumor Attributes NK NK NK NK NK NK NK NK NK NKG2C NK NK NK NK NK Jeffrey S. Miller, MD NK CD57+ Formation of Adaptive Memory NK Cells Correlated with reduced relapse risk and superior disease-free survival in HCT Unique Subset of Activated NK Cells Heightened Effector Function Enhance Persistence Resistant to Immune Checkpoint Pathways

12 NK Cell Proliferation NK Cell Proliferation Adaptive Memory NK Cells Resistance to Immune Checkpoint Pathways Retained Proliferation Potential of Adaptive Memory NK Cells Conventional NK Cells Adaptive Memory NK Cells

13 CD56 (NK cells) FATE-NK100 Realizing the Potential of Adaptive Memory NK Cells CMV+ Donor Apheresis T & B Cell Depletion mono NK mono mono NK NK NK NK mono 7-Day Ex Vivo Modulation FT Cytokine Feeder-free NK NK NK NK NK NK NK NK Day 0 Day 0 Post-Depletion Day 7 Programming CD3 (T cells) Conventional NK Cell Therapies Overnight (O/N) Cytokine-induced NK Cells FATE-NK100 Adaptive Memory NK Cells Cichocki et. al / CAN

14 FATE-NK100 Unique and Differentiated Properties of Adaptive Memory NK Cells NK cell product purity, potency and consistency NK cell maturation during product manufacture ( CD57, KIR, NKG2A, TIGIT) Tumor necrosis factor (TNF) and interferon (IFN)-γ cytokine production Direct cytotoxicity against tumor targets in vitro ADCC in combination with mabs against solid tumor targets in in vivo models In vivo persistence in preclinical models Tumor control in a xenogeneic model of ovarian cancer

15 FATE-NK100 Initial Clinical Observations VOYAGE Refractory / Relapsed AML Single IV infusion; accelerated dose-escalation; up to 3 dose levels 10-patient expansion at MTD Key read-outs: NK cell persistence; anti-leukemia activity; CRs Advanced through first two dose cohorts with no DLTs Dose Cohort 1 (1x10 7 TNC/kg) Dose Cohort 2 (2x10 7 TNC/kg) Age / Sex 67 / M 62 / F History Primary induction failure Relapsed; refractory to conventional NK cell therapy Leukemic Load 87% leukemic blasts in marrow 50% leukemic blasts in marrow Day 10 Persistence 76% of PB NK cells were of FATE- NK100 origin 95% of PB NK cells were of FATE- NK100 origin Day 14 Activity ~50% reduction in leukemic blasts Morphologic leukemia-free state (mlfs) Dose Cohort 3 (up to 1x10 8 TNC/kg) currently enrolling Not sustained following a single IV infusion

16 FATE-NK100 Launch of Multi-pronged Clinical Development Strategy VOYAGE Refractory / Relapsed AML Single IV infusion; accelerated dose-escalation; up to 3 dose levels 10-patient expansion at MTD Key read-outs: NK cell persistence; anti-leukemia activity; CRs Advanced through first two dose cohorts with no DLTs APOLLO Recurrent Ovarian Single IP infusion; accelerated dose-escalation; up to 3 dose levels 10-patient expansion at MTD Key read-outs: NK cell persistence; ORR by RECIST Advanced through first dose cohort with no DLTs; 2nd subject dosed DIMENSION mab Combination in Solid Tumors Single IV infusion; accelerated dose-escalation; up to 3 dose levels 3 parallel arms: mono; + trastuzumab; + cetuximab Key read-outs: NK cell persistence; ORR by RECIST Patient screening ongoing

17 Cell-based Cancer Immunotherapy Advantages of an Off-the-Shelf Cell Product Paradigm Key Features Today Tomorrow Cell Source Patient / Donor Cells Master Cell Line Genetic Engineering Random & Variable Precise & Complete Manufacturing Patient-specific Off-the-Shelf Product Consistency Heterogeneous Uniform & Well-defined Therapeutic Functionality Single MOA Multiple MOA Delivery Delayed & Uncertain On Demand Dose-per-Patient Single Multiple Overall Paradigm Patient-centric Product-centric

18 Human Induced Pluripotent Stem Cells Renewable Source for Off-the-Shelf Cell Products A Single Human Induced Pluripotent Cell Unlimited Self- Renewal On-Demand Immune Cell Derivation Robust Expansion Capacity Master Cell Banking Precise, Single-Cell Engineering Cell Line Validation Multi-faceted Functionality (e.g., Tumor Targeting, Cell Persistence, Checkpoint Resistance) Renewable Engineered Clonal Cell Lines ---> Clonal Cell Products

19 ipsc Product Platform Fate Therapeutics Transformative Approach to Cancer Immunotherapy Single ipsc Clone (Engineered) Single Pluripotent Stem Cell Renewable Propensity to differentiate into 200+ cell types Expansion & Banking Unlimited Supply of Clonal ipsc Master Cell Lines Master Cell Bank Working Cell Banks Working Cell Banks Working Cell Banks Differentiation & Expansion Thousands of Clonally-derived Doses of Cell Products Off-the-Shelf Homogeneous Multi-Dosing (Engineered) Cell Products

20 Off-the-Shelf NK- and T-Cell Products Collaborations with Top Investigators and Leading Centers 59 th American Society of Hematology (ASH) Annual Meeting December 9-12, 2017 in Atlanta, Georgia Clinical Translation of Pluripotent Cell-derived Off-the-Shelf NK Cell Cancer Immunotherapy Engineered Human ipscs with Novel CARs to Generate NK Cell Cancer Immunotherapies with Targeted Anti-Tumor Activity Generation of Clonal Antigen Specific CD8ab+ Cytotoxic T-Lymphocytes from Renewable Pluripotent Stem Cells for Off-the-Shelf T Cell Therapeutics Jeffrey S. Miller, MD Dan Kaufman, MD PhD Michel Sadelain, MD, PhD

21 Off-the-Shelf NK Cell Products Targeting Three 2018 INDs for Combination Therapy Clonal master ipsc line NK differentiation Homogenous cell product FT500 Master ipsc Line hncd16 insertion Clonal master ipsc line + hncd16 NK differentiation Homogeneous cell product FT516 Engineered Master ipsc Line hncd16 insertion / CD38 KO + hncd16 Clonal master ipsc line NK differentiation Homogenous cell product FT538 - CD38 Engineered Master ipsc Line

22 FT500 Manufacturing Robust Differentiation Protocol for ipsc-derived NK Cell Production 1 ipsc 100 CD34s 5L Grex Large clonal population of NK cells in a single production run capable of yielding hundreds of doses of homogeneous drug product for off-the-shelf delivery to patients

23 FT500 Biological Properties Comparative Gene Expression Analysis vs. Peripheral Blood NKs ink ink Round 1 ink Round 2 ink Round 3 Adult NK Adult NK Round 1 Adult NK Round 2 Adult NK Round PC icd34+ ipsc iprot CD7+ Fibroblast iprot CD ipsc icd34+ Fibroblast ireg CD14+ CD33+ iprot CD7- iprot CD7+ ANOVA = 0.01 FDR = 0.01 Fold Change (log 2 ) = 4 RMA-probe intensity (log 2 ) = >7 13,770 probes covering 8,508 unique genes PC 3 ireg CD CD PC

24 Tumor Killing FT500 Cell Potency ipsc-derived vs. Peripheral Blood NK Cells SKOV3 (Ovarian Cancer) Killing Assay Overnight Primed NK Cells Off-the-Shelf ink Cells Off-the-Shelf ink Cells

25 FT500 Purity No Residual ipscs in FT500 Cell Product Determination made analyzing a set of master pluripotency genes (NANOG, OCT4, SOX2, REX1) highly expressed in ipscs but not in background of NK cells No ipscs detected at the resolution of 1 in 2 million during multiple ink cell manufacturing runs

26 FT500 Production Technology Transfer to MCT cgmp Facility 1x10 6 ipscs delivers 1x10 12 NK cells during 44 day manufacturing process Molecular and Cellular Therapeutics 33,000 sf, free-standing, state-of-the-art GMP facility FT500 1x10 9 Cryopreserved Cells

27 FT500 in Combination with Checkpoint Inhibitors Synergy with T Cells to Infiltrate and Destroy 3D Tumor Mass

28 FT500 Proposed FIH Study Multiple Cycles of FT500 + Checkpoint Inhibitor Dosed Weekly Screening Window: Refractory Solid Tumors One Cycle Checkpoint Inhibitor Given per SOC dose and frequency until disease progression

29 FT516 Engineered hncd16+ NK Cell Product Candidate Mid-2018 IND Filing Expected for Monoclonal Antibody Combo Engineered high-affinity non-cleavable CD16 Fc Receptor FDA-approved Monoclonal Antibodies Modified form of CD16a IgG antibody-binding receptor resists shedding upon activation + hncd16 High affinity Cleavage resistant Bi- / Tri- Specific Engagers Renewable Engineered Pluripotent Cell Line Engineered hncd16 ink Cells for ADCC

30 Tumor Killing Tumor Killing FT516 Engineered hncd16+ NK Cell Product Candidate In Vitro ADCC for Solid Tumors SKOV3 (Ovarian) (HER2 hi /EGFR hi ) A549 (Lung) (HER2 lo /EGFR hi ) T im e (h o u r s ) T im e (h o u r s )

31 FT516 Engineered hncd16+ NK Cell Product Candidate In Vivo POC Luc-SKOV3 (Ovarian Cancer) Tumor Image Analysis Untreated Herceptin Herceptin + FT516 D4 Initiation of Day 5 D18 D

32 CD16 FT538 Engineered hncd16+ / CD38-null NK Cell Product 2H18 IND Filing to Complement Darzalex Therapy FT538 hncd16 insertion CD38 knock-out Single cell selected Master ipsc line generated Renewable Engineered Master Pluripotent Cell Line NK differentiation CD38 CD38 is expressed at high levels on myeloma cells As an IgG1 antibody, daratumumab is an ideal mediator of ADCC against CD38+ tumor cells NK cells, which are critical to ADCC-induced lysis of tumor cells, also express CD38 Clinical studies have shown that peripheral blood NK cell counts are reduced rapidly following daratumumab administration and remain low over the course of treatment

33 Off-the-Shelf T Cell Products Memorial Sloan Kettering Collaboration Dr. Michel Sadelain, MD, PhD Director, Center for Cell Engineering Memorial Sloan Kettering Cancer Center

34 Off-the-Shelf T Cell Products The Sadelain Roadmap Engineering therapeutic attributes into pluripotent cell lines is a breakthrough approach to renewably generate potent T-cell immunotherapies. This unique approach offers the prospect for off-the-shelf delivery of T-cell therapies with enhanced safety and therapeutic potential at the scale necessary to serve significant numbers of patients. From Autologous to Off-the-Shelf T Cell Therapy Single Cell Derived Off-the-shelf manufacturing from master pluripotent cell line Adapted from: Themeli, Riviere & Sadelain, Cell Stem Cells,

35 CAR19 Ex Vivo Generation of CAR19+ CD8αβ+ T Cells Generation from Clonal Engineered Master ipsc Line Parental hipsc Clonal CAR19 Master hipsc Line CAR+ hipsc Pool CAR+ Master Pluripotent Cell Line CAR19-iT cells CAR19 Clonal (from a single cell) Pluripotent Renewable (unlimited source) CD3 Homogenous population Reproducible Well-defined

36 ipsc-derived CAR19+ CD8αβ+ T Cells Global Gene Expression Comparison vs. Primary T Cells

37 FT819 CAR19 TCR-null T Cell Product Candidate Generated from Clonal Engineered Master ipsc Line TCR Disruption TRAC-encoded CAR Expression

38 FT819 CAR19 TCR-null T Cell Product Candidate Generation of ipsc-derived CD8αβ+ T Cells with Antigen Specificity % killing % killing Specific Cytotoxicity TRAC - 28 TRAC - 28 Nalm6 CD19+ Nalm6 CD19-/- Nalm6 CD19+ Nalm6 CD19-/ E:T E:T

39 Immuno-Regulatory Programs

40 ProTmune Transforming the Curative Potential of Allogeneic HCT A Next-Generation Hematopoietic Cell Graft to Prevent Acute Graft-versus-Host Disease ProTmune Small molecule programmed mobilized peripheral blood graft FT FT4145 Allogeneic HCT performed with curative intent Orphan hematologic malignancies (e.g., AML, ALL, MDS) Rare genetic disorders (e.g., β-thalassemia, sickle cell) Attractive market opportunity ~30,000 allogeneic HCT procedures performed annually Conducted at concentrated number of centers of excellence Significant unmet medical need Acute GvHD is leading cause of early morbidity and mortality 40-80% of patients experience Grades 2-4 acute GvHD No FDA approved therapies for prevention Immunosuppressive treatment can lead to infections / relapse

41 Acute Graft-vs-Host Disease High Incidence Rates during First 100 Days post-hct mpb, MAC, no TBI BM, MAC, TBI mpb, RIC, TBI mpb, MAC, TBI ~ 60% BM, RIC BM, MAC, no TBI Jagasia et al., Blood, CIBMTR centers ~ 60% Historical Incidence Rate (Grade 2 4)

42 Pathophysiology of Acute GvHD Tissue Damage Cytokine Storm IL-6 IL-1β TNF-α Conditioned Patient IFN-ᵞ T Cells Donor Donor Allo-reactive T-cell Activation Host APCs Tc17 Assault on Patient Tissue Immunosuppressive Agents IL-12 Th17 Severe Infections Th1 Tc1 Acute GvHD (gut, liver, skin) ~40-80% D100 cumulative incidence ~10-20% early mortality ~70% D100 cumulative incidence Relapse ~35% 1YR cumulative incidence

43 Acute Graft-vs-Host Disease Severe Acute GvHD Causes Mortality G1 G0 G2 G3 G4 Years since Transplantation

44 ProTmune The Next-Generation Hematopoietic Cell Graft ProTmune

45 ProTmune Ex Vivo Small Molecule Modulation of Donor T Cells Striking the Balance between GvHD and GvL Attenuated T-Cell Response to Cytokine Signaling (IL-6) Naïve T Cells Memory T Cells

46 ProTmune PROTECT Phase 1/2 Study for Prevention of Acute GvHD Phase 1 Stage: Day 28 Safety Assessment Allogeneic HCT Setting Matched unrelated donor (MUD) mpb HCT with myeloablative conditioning Hematologic malignancies include ALL, AML & MDS Standard-of-care GvHD prophylactic (Methotrexate / Tacrolimus) Seven subjects received ProTmune Safety Criteria Day 28 Engraftment without Graft Failure Day 28 Survival Day 28 Safety Assessment All subjects met the Day 28 safety objectives of neutrophil engraftment and survival All subjects reached Day 28 without any events of graft failure or SAEs related to ProTmune DMC unanimously recommended advancement into Phase 2 efficacy stage

47 ProTmune PROTECT Phase 1 Day 100 Efficacy Data # maximum grade GvHD

48 Randomized, Controlled, Blinded ProTmune PROTECT Phase 1/2 Study for Prevention of Acute GvHD Phase 2 Stage: 60 Subjects, Double-blinded, Randomized, Controlled Currently Enrolling at 14 U.S. Centers Fast Track Designation ProTmune Cell Graft (n=30) Standard-of-care mpb Cell Graft (n=30) Primary Endpoint Day 100 Cumulative Incidence of Grades 2-4 Acute GvHD Exploratory Endpoints Cancer Relapse; Severe Infections; Event-free Survival

49 ProTmune Next-Generation Graft to Prevent Acute GvHD Preventive approach to address leading cause of early morbidity and mortality 40 to 80% of patients undergoing allogeneic HCT experience acute GvHD Death directly attributable to acute GvHD or its treatment occurs in 10 to 20% of patients No approved preventive therapies in the U.S. Highly-differentiated therapeutic paradigm Optimize biological properties of donor hematopoietic cells ex vivo using small molecules On-site manufacture integrates into current clinical practice Avoids costly and time-consuming measures (e.g., genetic engineering, cell expansion, cell separation) Strong commercial positioning targeting significant market opportunity Matched unrelated donor (MUD) for hematologic malignancies is predominant HCT setting Composition of matter patents extending through 2032 Secured Fast Track in US and broad Orphan Drug Designations in US and EU

50 ToleraCyte Tolerizing the Immune System for Autoimmune Diseases A First-in-Class Immunoregulatory CD34 + Cell Product Candidate to Induce Immune Tolerance ToleraCyte Small molecule programmed CD34 + cells Autoimmune disorders result from malfunction of the body s natural defense systems Adaptive immune system (e.g., autoreactive T cells) mistakenly recognizes healthy cells as foreign and attacks and destroys the body s own tissue 80+ autoimmune disorders estimated to affect ~50M in U.S. Most common disorders include rheumatoid arthritis, lupus, inflammatory bowel disease, multiple sclerosis and type 1 diabetes CD8+ T cells (red) attacking pancreatic beta cells (green)

51 Fold Change (mrna) ToleraCyte Small Molecule Programmed CD34+ Cell Product Ex vivo modulation of CD34 + cells with two small molecules induces the expression of genes involved in cell migration and immune regulation Vehicle ToleraCyte

52 Immuno-Regulatory CD34 + Cell Therapy Collaborator Established Proof-of-Principle in Type 1 Diabetes Paolo Fiorina, MD, PhD Assistant Professor of Pediatrics, Harvard Medical School Hyperglycemic Mice Adoptive Transfer of PD-L1+ Hematopoietic Cells Extensive investigation into T-cell destruction of pancreatic beta cells Engineered PD-L1 hematopoietic cells to assess potential to exploit checkpoint axis Demonstrated that single administration of PD-L1+ cells revert hyperglycemia in preclinical model of T1D Days after Injection

53 Glycemia (mg/dl) Immuno-Regulatory CD34 + Cell Therapy Durable Disease Correction in T1D Mouse Model Hyperglycemic Mouse Small Molecules Blood Glucose Levels No Treatment Untreated (n=5) Vehicle-Treated HSPCs Programmed HSPCs plk cells (n=8) n= n= n= Normoglycemia Days after onset of hyperglycemia

54 Immuno-Regulatory CD34 + Cell Therapy Disease Attenuation in EAE Mice (Multiple Sclerosis) Programmed HSPCs attenuate loss of motor function in EAE Mice Loss of Motor Function

55 ToleraCyte Small Molecule Programmed CD34 + Cell Product for Autoimmunity Builds on clinical precedent for CD34+ cell therapy Use of patient- and donor-sourced CD34+ cells has well-established safety record Unique immuno-regulatory mechanism of action T-cell targeting approach through enhanced homing of programmed CD34 + cells to sites of inflammation Robust suppression of T cells through immune checkpoint pathways (e.g., PD-L1, IDO1) Induction of immune tolerance (T-cell anergy) Durable disease correction demonstrated in multiple models of immune disorders Single administration attenuates disease in murine model of type 1 diabetes Single administration attenuates disease in murine model of multiple sclerosis Successful pre-ind meeting supports clinical investigation Defined clear path to first-in-human testing in adult patients with T1D Scientific and clinical rationale for testing ToleraCyte in multiple immune indications

56 Myeloid-Derived Suppressor Cells (MDSCs) Immuno-Regulatory Cells With Unique Properties Defined as immature myeloid cells with potent suppressive activity CD33+/CD11b+, CD14+/CD66+, HLA-DR low Suppressive activity occurs through diverse mechanisms of action ARG, inos, IL10, Gal9, CD73, TGFb Inhibition of T, NK, DC cells Activation of regulatory T and B cells Activity triggered by pro-inflammatory environment (antigen independent) Challenging to produce commercially-viable product using patient- or donor-sourced cells

57 Myeloid-Derived Suppressor Cells (MDSCs) Advantages Relative to Other Immuno-Regulatory Cell Types Cell Type Cell Feature T Regs MSCs HSCs MDSCs Multiple anti-inflammatory mechanisms Able to induce long-term tolerance Antigen agnostic activation - Homing to site of inflammation (systemic delivery) - Scalable manufacturing Enabled using ipsc Product Platform

58 FT300 ipsc-derived MDSC Product Feature Anti-inflammatory activity triggered by local inflammatory environment (antigen independent) MDSC s capable of homing to site of inflammation HLA matching not required for antiinflammatory activity or cell persistence Scalable process for manufacturing drug product Cryopreserved drug product Homogenous drug product Benefit Efficacy across a variety of autoimmune diseases (antigen independent MOA) Systemic IV delivery with efficacy in the local inflammatory environment Enables off-the-shelf product (one drug for all patients) Cost-effective therapy available for large patient populations; ability to repeat dose Centralized manufacturing; drug product available on-demand at site of care Predictable safety and efficacy profile with high-quality drug product

59 N o r m a l i z e d e x p a n s i o n N o r m a l i z e d e x p a n s i o n FT300 In Vitro Activity Potent Suppressor of T-Cell Proliferation Across HLA Barriers CD4 + CD * * * * * * Activated T Cells FT300 + Activated T Cells * * Segmented by ratio of FT300 : Activated T Cells (5 independent donors for each ratio)

60 % o f C D 8 + T c e l l s % o f C D 4 + T c e l l s FT300 In Vitro Activity Potent Suppressor of T-Cell Cytokine Release Across HLA Barriers 4 0 IFNg TNFa 8 0 IL-2 CD * * * * * 4 0 * * * * * * * * CD * * * 2 0 * * 2 5 * * * * * 0 N o N o N o S t i m S t i m S t i m Activated T Cells FT300 + Activated T Cells * * Segmented by ratio of FT300 : Activated T Cells (5 independent donors for each ratio)

61 FT300 In Vivo Functionality Suppression of T Cells and Disease Activity in GvHD Model NSG Disease Severity % T Cells iv % H u m a n C D % Survival P e r c e n t s u r v i v a l % h C D C D 3 + C D 4 + C D C D l o GvHD Score G V H D S c o r e P< * * * T Cells * 7.5 x 10 6 * Injected to induce GvHD + FT x P=0.07 Days D a y s Survival 0 % Regulatory T Cells 8 * GvHD Score Survival T-Cell Analysis Days T i m e 0 T Cells T Cells + FT

62 FT300 Path to IND Next Steps Conduct Pre-IND meeting with FDA Already completed with oncology division for FT500 and FT516 (ipscderived NK cell products) Complete GMP manufacturing at Fate CMO Already underway for FT500 and FT516 Conduct GLP IND-enabling studies File IND ipsc product platform to be de-risked through filing of INDs for FT500 and FT

63 Financial Summary

64 Fate Therapeutics Financial Summary Three Months Ended September 30, Revenue R&D Expense G&A Expense $1.0M $8.6M $2.8M Operating Expense, Adjusted 2 $10.0M Cash & Cash Equivalents $112.2M Employees 76 Total Shares Outstanding M [1] Pro forma for Dec 2017 common stock financing. [2] Excludes $0.9M in stock-based compensation expense and $0.5M in Juno-related research expense. [3] Includes 14.1M shares of common stock from conversion of non-voting preferred stock

65 Fate Therapeutics First-in-Class Cellular Immunotherapy Pipeline IMMUNO-ONCOLOGY PROGRAM PRECLINICAL CLINICAL RIGHTS FATE-NK100 AML Phase 1 Worldwide FATE-NK100 Ovarian Phase 1 Worldwide FATE-NK100 Solid Tumor mab Combo Phase 1 Worldwide FT500 (ink Cell) OTS Checkpoint Inhibitor Combination Worldwide FT516 (Engineered hncd16 ink Cell) OTS Monoclonal Antibody Combination Worldwide FT538 (Engineered CD38- ink Cell) OTS Daratumumab Combination Worldwide FT819 (Engineered CAR19 it Cell) OTS Worldwide IMMUNO-REGULATION ProTmune Graft-versus-Host Disease Phase 2 Worldwide ToleraCyte Autoimmune Disorders Worldwide FT300 (imds Cell) OTS Worldwide OTS Off-the-Shelf using Clonal Master Induced Pluripotent Stem Cell (ipsc) Lines

66 Better Cells For Better Therapies